Biological Mechanisms of Paeonoside in the Differentiation of Pre-Osteoblasts and the Formation of Mineralized Nodules

Abstract

Paeonia suffruticosa is a magnificent and long-lived woody plant that has traditionally been used to treat various diseases including inflammatory, neurological, cancer, and cardiovascular diseases. In the present study, we demonstrated the biological mechanisms of paeonoside (PASI) isolated from the dried roots of P. suffruticosa in pre-osteoblasts. Herein, we found that PASI has no cytotoxic effects on pre-osteoblasts. Migration assay showed that PASI promoted wound healing and transmigration in osteoblast differentiation. PASI increased early osteoblast differentiation and mineralized nodule formation. In addition, PASI enhanced the expression of Wnt3a and bone morphogenetic protein 2 (BMP2) and activated their downstream molecules, Smad1/5/8 and β-catenin, leading to increases in runt-related transcription factor 2 (RUNX2) expression during osteoblast differentiation. Furthermore, PASI-mediated osteoblast differentiation was attenuated by inhibiting the BMP2 and Wnt3a pathways, which was accompanied by reduction in the expression of RUNX2 in the nucleus. Taken together, our findings provide evidence that PASI enhances osteoblast differentiation and mineralized nodules by regulating RUNX2 expression through the BMP2 and Wnt3a pathways, suggesting a potential role for PASI targeting osteoblasts to treat bone diseases including osteoporosis and periodontitis.

Trifloroside Induces Bioactive Effects on Differentiation, Adhesion, Migration, and Mineralization in Pre-Osteoblast MC3T3E-1 Cells

“…In the present study, we demonstrated that TriFs activates Smad1/5/8, inhibits GSK3β, and stabilizes β-catenin, leading to an increase in RUNX2 expression and nuclear accumulation during osteoblast differentiation. MAPKs and AKT signaling proteins are also known to regulate RUNX2 expression and transcriptional activity [ 2 , 3 , 31 ]. The present study demonstrated that TriFs activates JNK and p38 but not ERK and AKT.…”

“…Bone metabolism and homeostasis are tightly maintained through physiological responses associated with mesenchymal stem cell-derived osteoblast differentiation and maturation [ 1 ]. Osteoblast differentiation is induced and controlled through complex signaling pathways, primarily Wnt3a- and bone morphogenetic protein 2 (BMP2)-mediated signaling molecules, as well as mitogen-activated protein kinases (MAPKs) and AKT, which induce the expression of Runt-related transcription factor 2 (RUNX2) and regulate the transcriptional activity in osteoblast differentiation [ 2 , 3 , 4 ]. Consequently, osteoblast differentiation and maturation produce osteoids through synthesis and secretion to construct the bone matrix, which then leads to mineralization of the bone matrix filled around collagen rope containing dense and irregular crystals of hydroxyapatite that bestow rigidity to the bone [ 5 , 6 ].…”

Calycosin-7-O-β-Glucoside Isolated from Astragalus membranaceus Promotes Osteogenesis and Mineralization in Human Mesenchymal Stem Cells

“…As anabolic drugs, compounds isolated from plants have been investigated to prevent and cure bone diseases [ 19 , 20 , 21 ]. Previously, our group demonstrated the beneficial effects of various natural compounds from plants on osteoblast lineages [ 22 , 23 , 24 , 25 , 26 , 27 ]. In the present study, we demonstrated the osteogenic function of Caly obtained from A. membranaceus in human MSCs.…”

Effects of Triterpene Soyasapogenol B from Arachis hypogaea (Peanut) on Differentiation, Mineralization, Autophagy, and Necroptosis in Pre-Osteoblasts

“…Osteoblast differentiation and migration are required to form new bone and remodel old bone through the synthesis and secretion of the organic component of the bone matrix and bone matrix mineralization comprising hydroxyapatite [ 2 , 3 ]. The multiple signaling pathways associated with BMP2 and Wnt3a proteins tightly regulate osteoblast differentiation by upregulating the expression and activity of RUNX2, which is a core transcription factor in osteoblast differentiation [ 4 , 5 ]. Pathologically, the impairment and dysregulation of osteoblast differentiation lead to the pathogenesis of bone diseases such as osteoporosis and periodontitis [ 6 , 7 ].…”